BIOCHEMICAL-ANALYSIS OF MYELIN PROTEINS IN A NOVEL NEUROLOGICAL MUTANT - THE TAIEP RAT

Hemispheres, spinal cords, and sciatic nerves were taken from taiep, c arrier, and control rats at ages ranging from 1 day to 16 months. Abso lute myelin yields from CNS taiep tissues peaked at similar to 2 month s and then decreased until they reached a low but stable level. Myelin yield from the affected hemispheres expressed as a percentage of age- matched controls decreased continuously from 2 weeks until it reached a stable level of similar to 10-15%. The same was true for the spinal cords, but here the myelin yield reached a plateau at a slightly highe r percentage of 20-25%. in comparison with control rats, isolated CNS myelin fractions from the affected rats had a greater content of high molecular weight proteins. Western blot analyses of CNS homogenates re vealed that myelin basic protein (MBP), proteolipid protein, and 2',3' -cyclic nucleotide 3'-phosphodiesterase were all present but decreased to levels generally consistent with the deficiencies of myelin. Howev er myelin-associated glycoprotein (MAG) levels always were reduced muc h more than those of the other three myelin proteins, and at younger a ges the apparent molecular weight for MAG was increased in the mutants . Western blot analyses of sciatic nerve homogenates showed that the l evels of MBP, MAG, and Po were not significantly different in control and mutant animals. These results suggested an early hypomyelination o f the CNS, with peak levels of myelin at 2 months, followed by a prolo nged period of myelin loss, until a very low but stable myelin lever w as reached. The consistently greater loss of MAG, in comparison with o ther CNS myelin proteins, is different from most other hypomyelinating mutants in which MAG is relatively preserved in comparison with the p roteins of compact myelin. This might be due to microtubular abnormali ties in the taiep mutant interfering with transport of myelin proteins and having the greatest effect on MAG because of its most distal loca tion in the periaxonal oligodendroglial membranes.